“…we know there are some things we do not know”
– Donald Rumsfeld
“Nothing worth knowing is accessible to the mind”
– Woody Allen (Manhattan)
Phil Marley tells his story of the lab and beyond.
Gut Feelings
Phil Marley.
I never wanted to be a lumberjack: I always knew I was going to
be a scientist. The only real question was, what flavour?
I grew up surrounded by science. My home town,
Abingdon, was equidistant from the UK Atomic Energy
Authority’s laboratories at Harwell, the Rutherford high
energy physics laboratories at Culham (where the Joint
European Torus nuclear fusion project now is) and Oxford
University. My school was full of kids from scientific
parents and I was one. My father was a physicist, but I never
really knew much about his research because his PhD was
examined under the Official Secrets Act – even he was not
allowed to keep a copy – but it was something to do with
explosions and his time at Los Alamos during the war,
which was pretty exciting. With an older brother and twin
sister into genetics and maths, I was destined to be a scientist.
But when I finished school, I went to Germany to play
chess. My school had an unusual connection with a nuclear
research centre near Karlsruhe whose director was chessmad and each year sent a chess-playing student to work
there before going to uni. Not quite child labour, but in
1975, I found myself dividing my time between playing
chess, learning bad French from my supervisor (to this
day, my French has a Bretton dialect) and doing my first
research project – on the efficiency of air monitoring for
leaks of radioactive materials – americium, plutonium,
californium. Surreal.
I went to Cambridge University in 1975 to study chemistry,
but doing a bit of everything in the Natural Sciences degree
exposed me to all sorts of biological sciences I had not
experienced at school. I was instantly hooked.
Big influences back then were two tutors at Trinity College:
Mike Berridge, of IP3 and Ca2+ signalling fame, and Tom
Jessell, who was doing his PhD with Les Iversen at the MRC
Neurochemical Pharmacology Unit (NCPU) – he found
his research sufficiently unchallenging he was learning
Japanese in his spare time. Together with Les, a brilliant
and inspiring lecturer in neuropharmacology, they were
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responsible for opening my mind to the addictive attraction
of research. They taught me my first two rules: Rule 1 (the
Rumsfeld Rule): The unknown is infinitely fascinating; and
Rule 2: Do something that really switches you on. Their
excitement about their research was palpable and infectious,
yet for every question I asked them, they said they didn’t
know the answer. Tantalising stuff!
I graduated in Pharmacology in 1978 totally besotted with
neuropharmacology. After a summer working with Brian
Richardson on pancreatic beta-cells in Swiss drug company
Sandoz in Basel, I returned to Cambridge to do my PhD
(after resisting persuasive arguments that I should go to
Oxford to become Phil D. Marley, D. Phil.). My initial project,
on the pharmacology of dorsal root ganglion cells using
intracellular electrodes, did not go well – in part because
my lab was next to a lift which caused local earthquakes
every time someone used it and due to a falling out with
my supervisor. So after completing a Masters, I joined Piers
Emson at the NCPU and started studies on the gut peptides
vasoactive intestinal peptide (VIP) and cholecystokinin
(CCK) as potential neurotransmitters in the brain. It would
be over 20 years before I returned to electrophysiology.
Phil’s first research experiment, testing the efficiency of air
monitoring for radioactive particles in front of a ‘hot cell’
at the Euratom centre near Karlsruhe, 1975.
NCPU was research heaven: it was really humming. It had
been set up to research schizophrenia. Les Iversen scoured
the world recruiting the best postdocs with the latest
techniques and bringing them to Cambridge, and many
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Vol 40 No 2 August 2009
other outstanding people came on sabbatical. NCPU
students got exposed to the best-of-the-best by way of
people, ideas, technologies and resources. Everyone
worked long hours and weekends. It was an extended
family – we worked, ate and partied together. One day
the whole unit was in a mesmerised, catatonic state
after seeing the newly-released Apocalypse Now the
night before.
I remember my first NCPU paper because it was
accepted by Neuroscience Letters without change –
I naïvely thought this was normal, but it has not
happened since with my 101 other papers. Everything
at NCPU was done in front of world class researchers:
bad logic in research questions, poorly designed
experiments, low quality data and over-interpreted
results were instantly, publicly and ruthlessly exposed.
It was invaluable training for the competitive life of
medical research ahead and taught me Rule 3: Do it
well. Quality matters.
I came to Australia by accident. After my PhD, I
continued my neurochemical studies on the molecular
forms of CCK and gastrin in the brain for six months
with Jens Rehfeld at the Rigshospital in wonderful,
wonderful Copenhagen. This was filling in time before
going to Montreal for a postdoc with Bruce Livett. I
had met Bruce at the 1981 International Society for
Neurochemistry meeting in Nottingham where, still a
PhD student, I gave a symposium talk. Bruce attended
my talk and subsequently offered me a place in his lab
at McGill (to this day, I don’t think he knows I missed
his own symposium talk the day before mine). But
while I was in Denmark, he contacted me to say he had
accepted a position back in Melbourne and would I go
to Australia instead of Canada. I had a vague feeling
Montreal and Melbourne were about the same distance
from the UK and said yes. I accepted a Royal Society
Stothert Research Fellowship, took a one-way ticket to
Melbourne and flew straight into a firestorm.
I arrived here the day before Ash Wednesday 1983.
Instead of swapping the -1°C in London for the -25°C
of Montreal, I came to +43°C in Melbourne. And
Melbourne was burning.
What followed were 10 years in the Department of
Biochemistry at the University of Melbourne, a move
from the central to the peripheral nervous system
and from gut peptides in the brain to the role of
neuropeptides in regulating adrenaline release from
the adrenal medulla. But after years of intense study, I
was buggered if I could work out what adrenal opioid
peptides did. With my partners-in-crime in Bruce’s
lab, Steve Bunn (now in Dunedin), Jane Ward (now
in Pharmacology, University of Melbourne), Ken
Mitchelhill (unfortunately passed away recently), and
Zeinab Khalil (still at Melbourne), we drafted a template
for our papers with the title “Lack of effect of opioid
peptides on XXX in bovine adrenal chromaffin cells”
and just completed the blanks. The best part of Bruce’s
lab was the ‘cake-and-chatter’ lab group meetings – so
long as the cake we made was good, nobody minded
that the chatter only presented more negative data.
It was Ian Chubb who convinced me to apply for an
NHMRC Research Fellowship. He simply pointed out
that the worst thing the fellowship committee could
do was say no. So in 1985, I applied for my Research
Fellowship (equivalent to the current R.D. Wright),
John Funder took me under his wing and tutored
me for the interview, and I got the fellowship. I had
switched to a Queen Elizabeth II Fellowship in 1984
and moved onto my NHMRC Fellowship in 1986 – at
three years postdoc. Chubb taught me the Nike rule,
Rule 4: Just do it. Have a go, get involved.
Three activities based on the Chubb Rule had
enormous significance for me in future years. I became
department seminar coordinator – something I did
for the next 18 years. I became convenor for regular
meetings of Victorian NHMRC research fellows
(although largely social, we did talk real science: I
clearly remember a serious talk by John Ludbrook
on the cardiovascular consequences of crucifixion
at one Easter gathering). And I joined the second
messenger journal club run by Stella Clarke, Phil
Robinson and Marjorie Dunlop. These networking
activities introduced me to literally hundreds of
terrific researchers from all disciplines, outstanding
people who I drew on to help me in my research and,
subsequently, in my decision to leave lab science.
Above: Bruce Livett’s lab in the Department of Biochemistry, University
of Melbourne. From right: Bruce Livett, Elaine Kekorius, Steve Bunn, Jane
Ward, Phil Marley, Zeinab Khalil, David Small and unknown, c.1986.
Left: Radioimmunoassay of CCK in 900 rat brain samples:
PhD at the MRC Neurochemical Pharmacology Unit, Cambridge, 1980.
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After 10 years hiding my lack of
biochemistry knowledge by being the
token pharmacologist in a biochemistry
department, it was time to move on. OK,
it was only 50 metres to the Pharmacology
Department, but my 1993 move was not
without hiccups: the week before I moved,
the ceiling in the lab opposite my future
lab collapsed under the weight of dried rat
droppings, which had accumulated over
many years from feral rats in the ducts and
swelled with water from a leaking pipe.
My research refocussed on the
pharmacology of cell signalling in
neurones, using cell-permeant drugs to
interrogate the roles of kinases in receptorBack to electrophysiology 25 years on: Pharmacology in 2003. From left:
evoked exocytosis in chromaffin cells. My
Damian Wallace, Amanda Donald, visitor and Phil Marley with our patch rig.
13 years in Pharmacology brought two
key developments. One was an invitation
from Elspeth McLachlan in 1996 to become National experience in medical research. It was an enormous relief
Secretary of the Australian Neuroscience Society – a and greatly energising.
role I held for six years, the maximum permitted. The
I duly swapped my lab coat for a suit in December 2005
other was a strong relationship with Peter Dunkley in and moved to the dark side to become a public servant
Newcastle. Although Peter had adopted chromaffin cells for the Victorian Government – Manager of Biomedical
as a model for his kinase research and we shared many Research and Technology in the Department of Innovation,
collaborative studies, for me his key influence was as Industry and Regional Development. My role is to facilitate
a mentor. Bruce and Peter were my sounding boards, medical research in Victoria through developing policy that
advisors and guides throughout my lab research life and supports medical research and translation of research into
many was the time I depended on them to keep me going. health and commercial benefits, and through delivering
Rule 5: Get a mentor. Open, frank, fearless, trustworthy. programs that develop new facilities (such as the Parkville
In 2004, I needed an exit strategy. After 18 years in the Comprehensive Cancer Centre and extensions to the
NHMRC fellowship scheme and having been promoted to Walter and Eliza Hall Institute and the Burnet Institute)
PRF in 1998, I wanted to move on from the lab. I was 48 and assist research institutes with indirect costs. It’s a very
and felt I had gone as far as I could in a research career. different world from the lab, one captured with frightening
At the time, my lab was getting increasingly empowered accuracy by The Hollowmen, but it uses my knowledge
with siRNA techniques to knock down trimeric G proteins of the players and the game of medical research, and the
and patch-clamp electrophysiology (the first cell patched need for advanced technologies and skills. It also uses
on my rig was by Bert Sakmann, Nobel Prize winner as communication skills in educating and persuading my
co-inventor of patch-clamping). However, I was getting department and government to adopt certain positions or
more satisfaction from other activities: influencing policy actions. It is a very good fit for me.
on fellows’ careers, being a member of the Mental Health
My career has had no grand plan. I have not mapped
Research Institute’s scientific advisory committee, assessing where I am going, but have just followed my interests
grants on NHMRC review panels, managing the Australian and gut feelings. I did my PhD at the same uni I did my
Neuroscience Society and organising conferences. So in undergraduate studies (unusual in the UK), came to
December 2004, I announced publicly that I would close Australia by accident and moved 50 metres between
my lab in December 2005 and walk away from lab science. I departments as the sum total of my travels in over 22 years
have never regretted my decision.
in the lab. I have often followed the path of least effort and
I spent 2005 fact-finding. What could life outside the lab this has taken me where it has.
offer? After 22 years in the lab, I knew nothing of the real
In reflecting on my times in the lab, I am particularly
world. With guidance from a career counsellor, I drew proud of two papers, both reviews that highlight what we
on the generous advice and experiences of a wide range don’t know and question the evidence for what we think we
of people, many from the contacts I had made from my know. To me this is what research is all about. So perhaps
extensive networking activities: COOs and Directors of I should add a Julius Sumner Miller rule: Rule 6: Ask why
research institutes, CEOs of research collaboratives and is it so? Assess, evaluate, ask big questions, ask the right
commercialisation companies, CEOs and CSOs of biotech question.
companies, partners in venture capital firms, directors of
My rules continue to guide me in my new lab-less life.
research administration offices, associate deans and DVCs
of research, MDs of recruitment companies, government
executives, consultants and others. And I found there
were fabulous opportunities out there for someone with
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